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The striatum is essential for learning which actions lead to reward and for implementing those actions. Decades of experimental and theoretical work have led to several influential theories and hypotheses about how the striatal circuit mediates these functions. However, owing to technical limitations, testing these hypotheses rigorously has been difficult. In this Review, we briefly describe some of the classic ideas of striatal function. We then review recent studies in rodents that take advantage of optical and genetic methods to test these classic ideas by recording and manipulating identified cell types within the circuit. This new body of work has provided experimental support of some longstanding ideas about the striatal circuit and has uncovered critical aspects of the classic view that are incorrect or incomplete.The striatum is crucial for learning and decision-making. Cox and Witten provide an updated overview of the roles of different parts of the striatal circuit in learning and decision-making, showing how recent experiments support and contradict previous models.

In this study, the authors show that host microbiota play a key role in modulating microglia homeostasis. Germ-free mice or mice with only limited microbiota complexity displayed defects in microglial cell proportions and maturation, leading to impaired innate immune responses. The authors find that short-chain fatty acid signaling regulates these effects in vivo . As the tissue macrophages of the CNS, microglia are critically involved in diseases of the CNS. However, it remains unknown what controls their maturation and activation under homeostatic conditions. We observed substantial contributions of the host microbiota to microglia homeostasis, as germ-free (GF) mice displayed global defects in microglia with altered cell proportions and an immature phenotype, leading to impaired innate immune responses. Temporal eradication of host microbiota severely changed microglia properties. Limited microbiota complexity also resulted in defective microglia. In contrast, recolonization with a complex microbiota partially restored microglia features. We determined that short-chain fatty acids (SCFA), microbiota-derived bacterial fermentation products, regulated microglia homeostasis. Accordingly, mice deficient for the SCFA receptor FFAR2 mirrored microglia defects found under GF conditions. These findings suggest that host bacteria vitally regulate microglia maturation and function, whereas microglia impairment can be rectified to some extent by complex microbiota.

Hintiryan, Foster et al . present an online mouse cortico-striatal projectome describing projections from the entire cortex to dorsal striatum. Computational neuroanatomic analysis of these projections identified 29 distinct striatal domains. This connectomics approach was applied to characterize circuit-specific cortico-striatal connectopathies in a mouse model of Huntington disease and in monoamine oxidase (MAO) A/B knockout mice. Different cortical areas are organized into distinct intracortical subnetworks. The manner in which descending pathways from the entire cortex interact subcortically as a network remains unclear. We developed an open-access comprehensive mesoscale mouse cortico-striatal projectome: a detailed connectivity projection map from the entire cerebral cortex to the dorsal striatum or caudoputamen (CP) in rodents. On the basis of these projections, we used new computational neuroanatomical tools to identify 29 distinct functional striatal domains. Furthermore, we characterized different cortico-striatal networks and how they reconfigure across the rostral–caudal extent of the CP. The workflow was also applied to select cortico-striatal connections in two different mouse models of disconnection syndromes to demonstrate its utility for characterizing circuitry-specific connectopathies. Together, our results provide the structural basis for studying the functional diversity of the dorsal striatum and disruptions of cortico-basal ganglia networks across a broad range of disorders.

Modern decision neuroscience offers a powerful and broad account of human behaviour using computational techniques that link psychological and neuroscientific approaches to the ways that individuals can generate near-optimal choices in complex controlled environments. However, until recently, relatively little attention has been paid to the extent to which the structure of experimental environments relates to natural scenarios, and the survival problems that individuals have evolved to solve. This situation not only risks leaving decision-theoretic accounts ungrounded but also makes various aspects of the solutions, such as hard-wired or Pavlovian policies, difficult to interpret in the natural world. Here, we suggest importing concepts, paradigms and approaches from the fields of ethology and behavioural ecology, which concentrate on the contextual and functional correlates of decisions made about foraging and escape and address these lacunae.

In this Opinion article, Nutt and colleagues examine the history of and current evidence for the dopamine theory of addiction. They argue that dopamine's role in addiction is more complicated than the role that is put forward in this theory. For several decades, addiction has come to be viewed as a disorder of the dopamine neurotransmitter system; however, this view has not led to new treatments. In this Opinion article, we review the origins of the dopamine theory of addiction and discuss the ability of addictive drugs to elicit the release of dopamine in the human striatum. There is robust evidence that stimulants increase striatal dopamine levels and some evidence that alcohol may have such an effect, but little evidence, if any, that cannabis and opiates increase dopamine levels. Moreover, there is good evidence that striatal dopamine receptor availability and dopamine release are diminished in individuals with stimulant or alcohol dependence but not in individuals with opiate, nicotine or cannabis dependence. These observations have implications for understanding reward and treatment responses in various addictions.

Key Points Vulnerability to relapse that persists even after prolonged abstinence is a major problem in treating cocaine addiction. Mechanisms underlying this persistent vulnerability can be studied using rodent models of cue-induced cocaine craving during abstinence from cocaine self-administration. Cue-induced cocaine craving in rodents progressively intensifies (incubates) over the first month of abstinence and remains high for months. Incubation of craving also occurs in human drug users. Incubation of cocaine craving depends on an evolving series of neuroadaptations in the reward circuitry. Early adaptations in the ventral tegmental area and perhaps also the amygdala lead to more persistent changes in the nucleus accumbens, medial prefrontal cortex and central nucleus of the amygdala that increase the reactivity of neurons in these regions to cocaine cues and are ultimately required for the expression of incubated craving. Increased reactivity of these regions of the rodent brain to cocaine cues presented during abstinence is important because neuroimaging studies in human cocaine users have found that heightened cue reactivity in related brain regions is associated with addiction severity and risk of relapse. The relationship between cocaine craving and synaptic transmission has been most thoroughly studied in the nucleus accumbens, where abstinence is associated with changes in AMPA receptor subunit composition and silent synapse-based remodelling. Strengthening of excitatory synapses on nucleus accumbens neurons is particularly important for the maintenance of incubated craving after prolonged abstinence. Dopamine transmission is altered during abstinence owing to plasticity within the ventral tegmental area and changes in dopamine receptor expression in dopaminergic projection areas, but many questions remain about the role of dopamine transmission in modulating synaptic plasticity and behaviour during abstinence. Potential therapeutic strategies to prolong abstinence, identified through rodent studies, include the use of agonists of metabotropic glutamate receptor 2 (mGluR2) and/or mGluR3, mGluR1 positive allosteric modulators, serotonin (5-HT) receptor ligands (including 5-HT 1B receptor agonists, 5-HT 2C receptor agonists and 5-HT 2A receptor antagonists), D3 dopamine receptor antagonists, environmental enrichment and interventions to normalize sleep patterns. One of the greatest challenges in treating addiction is preventing relapse during abstinence. In this Review, Marina Wolf discusses rodent models of cocaine craving that reveal the synaptic plasticity that occurs in reward-related brain regions during the abstinence phase. Although it is challenging for individuals with cocaine addiction to achieve abstinence, the greatest difficulty is avoiding relapse to drug taking, which is often triggered by cues associated with prior cocaine use. This vulnerability to relapse persists for long periods (months to years) after abstinence is achieved. Here, I discuss rodent studies of cue-induced cocaine craving during abstinence, with a focus on neuronal plasticity in the reward circuitry that maintains high levels of craving. Such work has the potential to identify new therapeutic targets and to further our understanding of experience-dependent plasticity in the adult brain under normal circumstances and in the context of addiction.

Midbrain dopamine neurons are well known for their role in reward-based reinforcement learning. We found that the activity of dopamine axons in the posterior tail of the striatum (TS) scaled with the novelty and intensity of external stimuli, but did not encode reward value. We demonstrated that the ablation of TS-projecting dopamine neurons specifically inhibited avoidance of novel or high-intensity stimuli without affecting animals’ initial avoidance responses, suggesting a role in reinforcement rather than simply in avoidance itself. Furthermore, we found that animals avoided optogenetic activation of dopamine axons in TS during a choice task and that this stimulation could partially reinstate avoidance of a familiar object. These results suggest that TS-projecting dopamine neurons reinforce avoidance of threatening stimuli. More generally, our results indicate that there are at least two axes of reinforcement learning using dopamine in the striatum: one based on value and one based on external threat.

It is widely assumed that D1 and D2 dopamine receptor-expressing striatal neurons code for discrete pathways in the basal ganglia. Combining optogenetics and electrophysiology, the authors show that this output architecture does not apply to nucleus accumbens neurons. Current thinking attributing D1/D2 selectivity to accumbens projections thus should be reconsidered. It is widely accepted that D1 dopamine receptor–expressing striatal neurons convey their information directly to the output nuclei of the basal ganglia, whereas D2-expressing neurons do so indirectly via pallidal neurons. Combining optogenetics and electrophysiology, we found that this architecture does not apply to mouse nucleus accumbens projections to the ventral pallidum. Thus, current thinking attributing D1 and D2 selectivity to accumbens projections akin to dorsal striatal pathways needs to be reconsidered.

Key Points Research has begun to explore how age-related changes in the brain systems that are implicated in affect and motivation influence decision making. Older and younger adults show similar affective and neural sensitivity to anticipated financial gains during value assessment as well as to gain and loss outcomes. However, older adults show reduced affective and neural sensitivity to anticipated financial losses. Older adults make more suboptimal choices during financial risk taking, which seems to be related not to shifts in risk preference but rather to increased variability in nucleus accumbens (NAc) activity. Older adults make more optimal choices during delay discounting by assigning higher values to future gains, which appears to be related to increased NAc activity during consideration of future rewards. Older adults make more suboptimal choices when engaging in probabilistic reward learning. This seems to be related to decreased NAc activity associated with reward prediction errors (but not necessarily reward predictions), which may result from reduced medial prefrontal cortex input into striatal circuits. Understanding how ageing variably influences brain function and structure may better inform targeted interventions designed to improve decision performance in individuals of all ages. Ageing affects multiple aspects of brain structure and function, and therefore is likely to influence complex behaviours such as decision making. Samanez-Larkin and Knutson describe age-related changes in the affective and motivational circuits that drive choice, and consider how these influence decision making. As the global population ages, older decision makers will be required to take greater responsibility for their own physical, psychological and financial well-being. With this in mind, researchers have begun to examine the effects of ageing on decision making and associated neural circuits. A new 'affect–integration–motivation' (AIM) framework may help to clarify how affective and motivational circuits support decision making. Recent research has shed light on whether and how ageing influences these circuits, providing an interdisciplinary account of how ageing can alter decision making.

Insulin activates insulin receptors (InsRs) in the hypothalamus to signal satiety after a meal. However, the rising incidence of obesity, which results in chronically elevated insulin levels, implies that insulin may also act in brain centres that regulate motivation and reward. We report here that insulin can amplify action potential-dependent dopamine (DA) release in the nucleus accumbens (NAc) and caudate–putamen through an indirect mechanism that involves striatal cholinergic interneurons that express InsRs. Furthermore, two different chronic diet manipulations in rats, food restriction (FR) and an obesogenic (OB) diet, oppositely alter the sensitivity of striatal DA release to insulin, with enhanced responsiveness in FR, but loss of responsiveness in OB. Behavioural studies show that intact insulin levels in the NAc shell are necessary for acquisition of preference for the flavour of a paired glucose solution. Together, these data imply that striatal insulin signalling enhances DA release to influence food choices. Insulin signals satiety after a meal; however, the rising incidence of obesity and chronic insulin elevation suggests that insulin may also signal reward. Here, Stouffer et al . show that insulin amplifies dopamine release in rodent striatum depending on diet, and that striatal insulin can influence food choice.